We have made use of recombinant plasmids containing cloned globin cDNA sequences to study the organization of the human gamma-delta-beta globin gene locus. The predicted gene order has been confirmed, and polymorphisms were used to distinguish between the two gamma-globin genes and between the delta and beta globin genes. Clones were made containing the beta-globin genes from nuclear DNA isolated from patients with beta-zero and beta-plus thalassaemias. These show a normal restriction enzyme map, without deletions. Sequencing, in vitro transcriptional analysis, and in vivo expression are being studied in order to attempt to determine the differences causing the thalassaemic lesions. The linkage of non-selected restriction site polymorphisms to thalassaemias was studied in different populations. It is possible to use such polymorphisms for antenatal diagnosis of beta-thalassaemias on a case-by-case basis, particularly in the Italian community.